Squamous cell carcinoma (SCC) is the most common malignancy of the oral cavity. Failure to diagnose and treat early lesions, despite their well defined histopathologic criteria and accessibility to clinical detection, underlies the advanced presentation and the significant morbidity and mortality of patients with this cancer. Since the development and progression of neoplasms result from continuous accumulation of various genetic alterations, identifying genetic markers associated with early, intermediate and advanced oral squamous lesions will have important diagnostic and clinical implications. p53 gene and, based on our preliminary data, selected chromosomal loci with emphasis on the refined mapping of 3p21, 8p21, 9p21 and 11p15.5 regions by microsatellite markers will be analyzed on microdissected samples of normal and dysplastic epithelium and invasive lesions from each specimen. In the first phase of the study, samples from 100 retrospective cases will form our materials to determine the highest and most consistent markers for each pathomorphologic stage. In the second phase, each of 20/year prospectively resected specimens will be carefully and systematically mapped for multiple spatially separate samples of normal, different pre- malignant epithelium and malignant lesions to determine clonal progression, stability and heterogeneity of the selected markers. The results will be correlated with histopathologic progression, aggressive tumor characteristics and epidemiological factors.